In a simplified formulation, an elevated blood pressure is the result of an alteration in volume homeostasis and/or vascular reactivity. In such a scheme, the cardiovascular system and the kidney are critical components in maintaining normal blood pressure. However, cardio-vascular and renal responses are modulated by a variety of agents (homones) which include aldosterone, angiotensin II, bradykinin, ADH, and epinephrine. The objective of this proposal is the definitive assessment of two key regulatory systems, the renin-angiotensin-aldosterone and kallikrein-bradykinin systems. Angiotensin II plays a pivotal role since it modulates both vascular reactivity and volume homeostasis. Recent studies suggest that the receptors for angiotensin II on the adrenal glomerulosa, the juxtaglomerular apparatus, the renal vascular bed and the general vascular bed are functionally different. An alteration in the normal responsiveness of these various classes of receptors could lead to an imbalance in volume homeostasis or in vasoconstrictor forces, thus producing an elevated blood pressure. This possibility will be evaluated by simultaneous assessment of the responses of these receptors to infused angiotensin II and synthetic analogues, e.g., competitive inhibitors of angiotensin II in normal subjects and patients with hypertension under carefully defined conditions of sodium and potassium balance. Since bradykinin is the most potent vasodilator produced endogenously, and since kallikrein (an activator of bradykinin) excretion has been reported to be decreased in some hypertensive studies, the kallikrein-bradykinin system will be evaluated in a parallel fashion with the renin-angiotensin system in normal and hypertensive subjects. Thus, this proposal is designed to provide a comprehensive investigation of these hormonal factors which may be involved in the pathophysiology of hypertension. A more complete understanding of these factors could lead to more rational therapeutic modalities.